Relationship between the use of hair products and urine benzophenone-3: the Korean National Environmental Health Survey (KoNEHS) cycle 4

Article information

Ann Occup Environ Med. 2024;36.e20

Publication date (electronic) : 2024 August 06

doi : https://doi.org/10.35371/aoem.2024.36.e20

, Jisoo Kang

Department of Occupational and Environmental Medicine, Soonchunhyang University Gumi Hospital, Gumi, Korea.

Correspondence: Seong-yong Cho. Department of Occupational and Environmental Medicine, Soonchunhyang University Gumi Hospital, 179 1Gongdan-ro, Gumi 39371, Korea. 97blueciel@naver.com

Received 2024 February 05; Revised 2024 June 03; Revised 2024 June 12; Revised 2024 June 13; Revised 2024 June 13; Accepted 2024 June 18.

Abstract

Background

Benzophenone-3 is a type of ketone with 2 benzene rings attached to a carbonyl group (C=O) and one benzene ring attached to a hydroxyl group (-OH). As an endocrine-disrupting chemical, benzophenone-3 is known to be associated with reproductive, developmental, thyroid, and endocrine toxicities. Benzophenone-3 is commonly used in hair products, cosmetics, and ultraviolet (UV) filters because of its characteristic property to absorb UV light. This study aims to investigate the association between the use of hair products and urine benzophenone-3 using the data from the Korean National Environmental Health Survey (KoNEHS) cycle 4 (2018–2020), which represents the Korean population.

Methods

Using the KoNEHS cycle 4 survey, the data of 3,796 adults aged ≥ 19 years were analyzed. Based on the 75th percentile concentration of urine benzophenone-3, the participants were divided into the low- and high-concentration groups. Chi-square test was conducted to analyze the association of urine benzophenone-3 with distribution of general characteristics, use of personal care products, consumption of marine foods, and use of plastic products as the variable. Logistic regression analysis was conducted to calculate odds ratios (ORs) for the high-concentration group of urine benzophenone-3 based on the use of hair products.

Results

Women with < 6 times or ≥ 6 times of hair product usage had significantly higher adjusted ORs compared to those who did not use hair products. The calculated ORs were 1.24 (95% confidence interval [CI]: 1.12–1.38) for women with < 6 times of usage and 1.54 (95% CI: 1.33–1.79) for women with ≥ 6 times of usage.

Conclusions

This study revealed the association between the use of hair products and the concentration of urine benzophenone-3 in the general Korean population.

Keywords: Benzophenone-3; Oxybenzone; Hair preparation; Cosmetics; Korean National Environmental Health Survey

BACKGROUND

Benzophenone-3 is a type of ketone with 2 benzene rings attached to a carbonyl group (C=O) and one benzene ring attached to a hydroxyl group (-OH).1 2 3 Among various benzophenone derivatives, benzophenone-3 is commonly found in the human matrix such as urine, blood, and breast milk.2 4 5 However, benzophenone-3 has recently been reported to be an endocrine-disrupting chemical with a negative impact on the human body2 6 as well as the aquatic ecosystem when released into the river and sea.4 5 7 8

Benzophenone-3 has a characteristic property to absorb ultraviolet (UV) A (320–340 nm), UVB (290–320 nm), and UVC (200–280 nm) rays.9 10 Because of this property and low cost, benzophenone-3 is commonly used in hair products, cosmetics, UV filters, textiles, fibers, plastics, and paints.2 9 11 12 Hair products include products for cleansing, conditioning and treatment, hair styling, coloring and bleaching, and perming or relaxing.13 Benzophenone-3 is added to hair products to protect the skin and prevent the degradation of hair product components.

So far, many studies have reported on the association of urine benzophenone-3 with UV filters, make-up products, lotions, and plastic containers, but only few studies have investigated the association between urine benzophenone-3 and hair products.14 15 16 17 18 In addition, previous studies were based on small number of participants14 16 18 and have focused on comparing urine benzophenone-3 concentration of personal care product users with nonusers while overlooking the frequency of use.16 Therefore, this study aims to determine the association between the urine benzophenone-3 and the use of hair products in general Korean population using the data of the Korean National Environmental Health Survey (KoNEHS) cycle 4 (2018–2020), a nationwide survey.

METHODS

Study participants

This study analyzed the KoNEHS cycle 4 data collected from 2018 to 2020. The KoNEHS is a nationwide legal investigation conducted by the Ministry of Environment and National Institute of Environmental Research at 3-year intervals from 2009.19 The participants of the KoNEHS were 4,239 adults aged ≥ 19 years. In this study, 443 participants with missing values of the main variables and urine creatinine level outside the range of 0.3–3.0 g/L were excluded. Finally, 3,796 participants were analyzed (Fig. 1).

Fig. 1

Flow chart of the selection of study participants.

KoNEHS: Korean National Environmental Health Survey.

Urine benzophenone-3 concentration

The KoNEHS included the data of urine benzophenone-3 concentration. From each participant who signed the informed consent for human-derived material research, 50–75 mL of urine sample was collected in a 125-mL sterile specimen cup. Urine samples which had ≤ 36 mL were noted as insufficient amount. The collected urine samples were transferred to an opaque container to be left on iced water for 20 minutes in a shaded area to lower the sample temperature. The samples were stored at −70°C until use in subsequent analyses. From the urine samples, benzophenone-3 was isolated and quantitatively analyzed using the API Triple Quad 5500 high-performance liquid chromatography/mass spectrometer of AB Sciex. The limit of detection for urine benzophenone-3 was 0.129 μg/L. Internal quality control was carried out daily in order to manage precision and accuracy. Precision control was used to analyze the consistency of the testing method. Relative standard deviation of 2 low-volume standard solution was less than 15% within batch and less than 20% between batches. For accuracy control, quality control sample was selected. Analytical concentration was established after correcting values of recovery rate, dilution factor, and standard solution measurements.19

Use of hair products

In the KoNEHS questionnaire, the use of hair products was assessed using the following categories: No use, once or no use per month, 2-to-3 times per month, 1-to-2 times per week, 3-to-5 times per week, and every day (6 or 7 times per week). In this study, the participants who responded no use were placed in the ‘No use’ group; those who responded once or no use per month, 2-to-3 times per month, 1-to-2 times per week, and 3-to-5 times per week usage were placed in the “< 6 times of use” group; and those who responded every day (6 or 7 times per week) were placed in the “≥ 6 times of use” group. Hair products include hair gel, hair spray, hair mousse, hair wax, hair serum and hair dye. Shampoo, hair cleanser and hair treatment were not included in hair products and were categorized under body cleansers.19 20

Potential confounders

The confounders in this study included general characteristics, use of perfumes, body-cleansing products, make-up products, manicure products, antimicrobial products, fragrance products, and UV filters that are known to contain benzophenone-3.2 10 11 12 21 The frequency of consumption of crustacean, fish, seaweed, shellfish, or other seafood was also included as benzophenone-3 has been detected in the marine environment and organisms.4 5 9 11 22 23 Additionally, the use of clear plastic containers for storing cooked food or boiled water and the frequency of drinking from polyethylene terephthalate (PET) bottles or plastic bags were included.2 5 9

Statistical analysis

Chi-square test was conducted to analyze the association of urine benzophenone-3 in participants with distribution of general characteristics, use of personal care products, consumption of marine foods, and use of plastic products as the variable. The concentration of urine benzophenone-3 was then divided by quartile, and based on the 75th percentile concentration of each total, men and women, the low- and high-concentration groups were classified.20 24 To calculate odds ratio (ORs) for the high-concentration group of urine benzophenone-3 based to the use of hair products, logistic regression analysis was conducted. Further, complex sample analysis was used to consider the stratification, clustering, and weighted variables.19 IBM SPSS version 28 for Windows (IBM Corp., Armonk, NY, USA) was used, and the significance level was set at p < 0.05.

Ethics statement

This study received approval from the Institutional Review Board (IRB) of Soonchunhyang University Gumi Hospital (IRB No. 2024-01-01).

RESULTS

Table 1 presents the general characteristics of the participants. Among a total of 3,796 participants, 1,780 (46.9%) were men, and 2,016 (53.1%) were women. The urine benzophenone-3 concentration was higher in women (17.0 ± 0.9 μg/g Cr) than in men (8.8 ± 0.2 μg/g Cr). The total, men and women group were then divided into 4 quartiles according to the 25th percentile, 50th percentile, 75th percentile urine benzophenone-3 concentration group. Men were higher in proportion of those with ≥ 25 body mass index (kg/m²) and current smoker status than in women. Women were higher in proportion of those who used ≥ 6 times of hair products, perfumes, body-cleansing products, make-up products, manicure products, antimicrobial products, fragrance products, and UV filters than men. A higher proportion of men used PET bottles or consumed crustacean, shellfish, or other seafood more than once per month than women. Also, men were higher in proportion of those who used clear plastic containers for storing boiled water more than once per month than women.

Table 1

General characteristics of the participants

Table 2 shows the distribution of urine benzophenone-3 according to each variable in the high and low concentration groups classified according to the 75th percentile concentration of urine benzophenone-3 (total: ≥ 1.73 μg/g Cr, male: ≥ 1.06 μg/g Cr, female: ≥ 2.51 μg/g Cr). The mean age of women was higher in the high-concentration group than in the low-concentration group. In women, the proportion of high concentration group of urine benzophenone-3 increased with frequent use of hair products, make-up products, manicure products, and UV filters. In men, the proportion of high concentration group of urine benzophenone-3 increased with frequent use of perfumes. In both men and women, the proportion of high concentration group of urine benzophenone-3 increased with frequent consumption of drinking from PET bottles.

Table 2

General characteristics of participants according to urinary benzophenone-3 based on gender

The association between use of hair products and urine benzophenone-3 concentration in total participants, men and women was evaluated by scatter plot in Fig. 2. Fig. 2A shows 75th percentile concentration in total (no use: 1.38 μg/g Cr, < 6 times of use: 2.13 μg/g Cr, ≥ 6 times of use: 2.73 μg/g Cr). Fig. 2B shows 75th percentile concentration in men (no use: 1.04 μg/g Cr, < 6 times of use: 1.10 μg/g Cr, ≥ 6 times of use: 1.22 μg/g Cr). Fig. 2C shows 75th percentile concentration in women (no use: 2.00 μg/g Cr, < 6 times of use: 2.92 μg/g Cr, ≥ 6 times of use: 3.72 μg/g Cr). Supplementary Table 1 shows quartile concentration of benzophenone-3 according to the use of hair products in total, men and women.

Fig. 2

Scatter plot of urine BP3 concentration vs. use of hair products.

(A) Scatter plot of urine BP3 concentration vs. use of hair products in total participants (n = 3,796). (B) Scatter plot of urine BP3 concentration vs. use of hair products in men (n = 1,780). (C) Scatter plot of urine BP3 concentration vs. use of hair products in women (n = 2,016).

BP3: benzophenone-3.

Analysis of variance was used to calculate the mean concentration of urine benzophenone-3. The mean concentration of urine benzophenone in total participants were 7.8 ± 0.2 μg/g Cr (no use), 21.5 ± 1.6 μg/g Cr (< 6 times of use), 16.6 ± 0.5 μg/g Cr (≥ 6 times of use) (p < 0.001). The mean concentration of urine benzophenone in men were 6.5 ± 0.1 μg/g Cr (no use), 20.6 ± 0.5 μg/g Cr (< 6 times of use) and 0.9 ± 0.0 μg/g Cr (≥ 6 times of use) (p < 0.001). The mean concentration of urine benzophenone in women 10.1 ± 0.6 μg/g Cr (no use), 22.1 ± 2.8 μg/g Cr (< 6 times of use) and 24.4 ± 0.8 μg/g Cr (≥ 6 times of use) (p < 0.001).

Table 3 shows the calculated OR values for high urine benzophenone-3 concentration according to the frequency of using hair products. The value of OR was higher in women with higher frequency of using hair products. The adjusted OR values were 1.24 (95% confidence interval [CI]: 1.12–1.38) in the group with < 6 times of use and 1.54 (95% CI: 1.33–1.79) in the group with ≥ 6 times of use. The OR values were not significant in men. Furthermore, additional OR values for urine benzophenone-3 concentration according to the 50th percentile concentration, with the frequency of using hair products are detailed in Supplementary Table 2.

Table 3

Adjusted odds ratios and 95% confidence interval of use of hair products with high concentrations of urine benzophenone-3

DISCUSSION

This study investigated the association between the use of hair products and urine benzophenone-3 concentration. The results showed that women with hair product usage of < 6 times or ≥ 6 times had a higher OR for high urine benzophenone-3 concentration than women with no usage of hair products. In a study involving 168 Korean adults who used cosmetic products containing benzophenone-3, urine benzophenone-3 concentration was higher in users (0.00576 μg/g Cr) than nonusers (0.00292 μg/g Cr).16 In a study using data from the National Health and Nutrition Examination Survey to represent the general US population, the mean concentration of urine benzophenone-3 in the group who never uses sunscreen was 9.3 µg/g Cr, while in the group who always used sunscreen was 116.8 µg/g Cr.17 The results of these previous studies were in line with the results of this study. So, urine benzophenone-3 can be used as a key indicator in the assessment of exposure to benzophenone-3 through hair products.

As an endocrine-disrupting chemical, benzophenone-3 is known to be associated with reproductive toxicity, developmental toxicity, thyroid toxicity, and endocrine toxicity.2 25 26 Benzophenone-3 is also known to be associated with uterine fibroids,27 endometriosis,28 hypothyroidism,2 3 29 30 lung cancer,31 and precocious puberty in both boys and girls.32 33 34 Also, benzophenone-3 can induce skin irritation,35 photoallergic contact dermatitis,36 and cheilitis.37

Benzophenone-3 is used in hair products as it can absorb UV light to prevent degradation of hair products and protect the skin. According to a study conducted in the US, benzophenone-3 was found in 8 out of 279 shampoos (2.9%), 7 out of 231 conditioners (3.0%), and 25 out of 286 hair-styling products (9.0%).38 In another study investigating 4,489 hair-care products registered in an online shop, < 10% of benzophenone-3 was detected in 1,363 conditioners (30.3%), 1,479 hair-styling products (32.9%), and 53 other hair products (1.2%).39 Among aerosol hairsprays, 0.014% of benzophenone-3 was detected, and pump hairsprays had up to 0.05% of benzophenone-3.40 Therefore, as hair products contain varying concentrations of benzophenone-3, the risk of benzophenone-3 exposure when using hair products cannot be ignored.

The routes of human exposure to benzophenone-3 include skin absorption,2 4 41 food intake,42 43 and respiratory inhalation.7 Among them, the main route is skin absorption.2 4 44 When applying benzophenone-3 to skin for 4 hours, the skin permeability was 35%.40 In another study, after 30 minutes of skin application, benzophenone-3 was detected in the stratum corneum at 4% of the applied amount.40 When hair products are used, benzophenone-3 can be absorbed through the scalp and forehead. Because, first, benzophenone-3 has low volatility due to its low vapor pressure at ambient temperature (0.0005 Pa at 20°C).45 Hence, benzophenone-3 can stay attached to the scalp for a long time with low evaporation. Based on Fick’s law of diffusion stating that particles move from a high concentration area to a low concentration area, benzophenone-3 on the scalp permeates into the stratum corneum, skin surface lipid, and viable epidermis.46 Second, the scalp and forehead exhibit more pores than other skin areas, with the scalp having particularly large pores, allowing ready permeation of lipophilic materials.47 48 Benzophenone-3 can easily permeate into the scalp and forehead due to its lipophilic property, reflected on the logarithmic n-octanol/water partition coefficient (LogKow) of 4.0.2 5 18 25 Therefore, the use of hair products that contain benzophenone-3 enables the absorption of benzophenone-3 through the scalp and forehead.

The components in hairspray products are released in the form of aerosol.40 Approximately 85% of aerosol particles attach to the scalp and forehead upon a single spray.49 50 It is known that aerosols with aerodynamic equivalent diameter (d_a ) < 10 μm can reach the lungs.49 However, the d_a of pump-type hairspray aerosol is 60–80 μm and that of propellant hairspray is 25–50 μm.40 49 51 Hence, 95–99% of the hairspray aerosols exhibit d_a > 10 μm.40 49 Therefore, benzophenone-3 in hairsprays is unable to enter the lungs and become deposited in nasopharyngeal and bronchial regions.40 49 50 Consequently, benzophenone-3 in hairspray is absorbed through the lungs to a limited extent, highlighting the importance of exposure via skin absorption.

Benzophenone-3 is metabolized mainly in the liver via Phases I and II.2 41 52 Phase I involves hydroxylation, oxidation, and reduction, whereby various benzophenone derivatives are generated.2 18 53 Phase II involves a conjugation process to increase the water solubility of benzophenone and allow its release in urine.2 18 53 Benzophenone-3 is detected in urine 3 hours after skin absorption,54 while the blood benzophenone-3 concentration reaches its maximum after 4 hours.53 The scalp, in particular, may show a rapid increase in blood benzophenone-3 considering its high vascularity.55 It is thus presumed that, while benzophenone-3 is rapidly absorbed, the relatively long biological half-life of approximately 79.2 hours10 56 implies that repeated use of hair products would lead to a continuous influence of benzophenone-3.3 57

In this study, the association between urine benzophenone-3 and hair products was observed in women only. In a study conducted in China, the level of benzophenone-3 detected in hair was higher in women than in men, attributed to the more frequent use of hair products and longer hair length in women.58 59 So, we presumed that urine benzophenone-3 was associated with only women, who applied a greater amount of hair products than men during a single use. Likewise, higher concentrations of benzophenone-3 were found in women than in men in this study. First, in this study, urine benzophenone-3 was calculated by dividing it with urine creatinine concentration for adjustment for urine dilution. Due to low urine creatinine concentration in women, urine benzophenone-3 concentration was higher in women.60 Second, women apply greater amount of cosmetics including hair products, UV filters, and make-up products than men, which inevitably increases urine benzophenone-3 concentration.58 59

The limitations of this study are as follows. First, as a cross-sectional investigation, this study was limited in clearly identifying the cause-effect relationship. Second, work-related variables such as the work environment and wearing of protective gear were not analyzed in this study. Third, the type and amount per use of hair products were unknown so that the level of exposure could not be accurately estimated. Specifically, the definition of hair products was not clear so this could have caused the possibility of occurrence of exposure inaccuracies. Lastly, as the data in this study were based on a questionnaire, the potential for deviation according to the memory and recall of participants cannot be ignored.

To the best of our knowledge, no large-scale study has been conducted on the association of use of hair products with urine benzophenone-3 in the South Korean population. This study is thus significant in determining the association between hair products and urine benzophenone-3 using data representative of general Korean population. Based on this study, continuous monitoring of benzophenone-3 exposure through the use of hair products is necessary.

Acknowledgements

This study used the Korean National Environmental Health Survey Cycle 4 (2018–2020), made by National Institute of Environmental Research (NIER-2020-01-01-016). We appreciate National Institute of Environmental Research for making the raw data of Korean National Environmental Health Survey available.

Notes

Funding: This research was supported by the Soonchunhyang University Research Fund and Inha University Hospital’s Environmental Health Center for Training Environmental Medicine Professional funded by the Ministry of Environment, Republic of Korea (2024).

Competing interests: The authors declare that they have no competing interests.

Authors contributions:

Conceptualization: Kim S, Cho SY.
Data curation: Kim S, Kang J, Huh SW.
Formal analysis: Kim S, Park HW.
Investigation: Cho SY.
Methodology: Yoon S.
Software: Kim S, Cho SY, Kang J.
Validation: Kim S, Cho SY, Kim D.
Writing - original draft: Kim S, Cho SY.
Writing - review & editing: Kim S, Cho SY.

Abbreviations

BMI

body mass index

BP3

benzophenone-3

confidence interval

creatinine

KoNEHS

Korean National Environmental Health Survey

IRB

Institutional Review Board

odds ratio

PET

polyethylene terephthalate

ultraviolet

References

1. Lago AF, Jimenez P, Herrero R, Dávalos JZ, Abboud JL. Thermochemistry and gas-phase ion energetics of 2-hydroxy-4-methoxy-benzophenone (oxybenzone). J Phys Chem A 2008;112(14):3201–3208. 18341312.

2. Yao YN, Wang Y, Zhang H, Gao Y, Zhang T, Kannan K. A review of sources, pathways, and toxic effects of human exposure to benzophenone ultraviolet light filters. Eco Environ Health 2024;3(1):30–44. 38162868.

3. Mustieles V, Balogh RK, Axelstad M, Montazeri P, Márquez S, Vrijheid M, et al. Benzophenone-3: comprehensive review of the toxicological and human evidence with meta-analysis of human biomonitoring studies. Environ Int 2023;173107739. 36805158.

4. Mao JF, Li W, Ong CN, He Y, Jong MC, Gin KY. Assessment of human exposure to benzophenone-type UV filters: a review. Environ Int 2022;167107405. 35843073.

5. Kim S, Choi K. Occurrences, toxicities, and ecological risks of benzophenone-3, a common component of organic sunscreen products: a mini-review. Environ Int 2014;70:143–157. 24934855.

6. Muncke J. Endocrine disrupting chemicals and other substances of concern in food contact materials: an updated review of exposure, effect and risk assessment. J Steroid Biochem Mol Biol 2011;127(1-2):118–127. 21073950.

7. Wan Y, Xue J, Kannan K. Occurrence of benzophenone-3 in indoor air from Albany, New York, USA, and its implications for inhalation exposure. Sci Total Environ 2015;537:304–308. 26282764.

8. Ye X, Kuklenyik Z, Needham LL, Calafat AM. Quantification of urinary conjugates of bisphenol A, 2,5-dichlorophenol, and 2-hydroxy-4-methoxybenzophenone in humans by online solid phase extraction-high performance liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem 2005;383(4):638–644. 16132150.

9. DiNardo JC, Downs CA. Dermatological and environmental toxicological impact of the sunscreen ingredient oxybenzone/benzophenone-3. J Cosmet Dermatol 2018;17(1):15–19. 29086472.

10. Wnuk W, Michalska K, Krupa A, Pawlak K. Benzophenone-3, a chemical UV-filter in cosmetics: is it really safe for children and pregnant women? Postepy Dermatol Alergol 2022;39(1):26–33. 35369611.

11. Sánchez-Quiles D, Tovar-Sánchez A. Are sunscreens a new environmental risk associated with coastal tourism? Environ Int 2015;83:158–170. 26142925.

12. Ro KW, Choi JB, Lee MH, Kirn JW. Determination of salicylate-and benzophenone-type sunscreen agents in cosmetic products by gas chromatography-mass spectrometry. J Chromatogr A 1994;688(1-2):375–382.

13. Gray J. Hair care and hair care products. Clin Dermatol 2001;19(2):227–236. 11397601.

14. Oh S, Ho S, Kim H, Lee S, Park N, Kho Y. Urinary concentrations of benzophenones in university students and association with cosmetics habits. Korean Journal of Environmental Health Sciences 2013;39(6):505–512.

15. National Institute of Food and Drug Safety Evaluation (KR). A study of analysis for hazardous materials in human urine – biomonitoring of benzophenones Updated 2014. Accessed January 4, 2024. https://scienceon.kisti.re.kr/commons/util/originalView.do?cn=TRKO201500007418&dbt=TRKO&rn= .

16. Ko A, Kang HS, Park JH, Kwon JE, Moon GI, Hwang MS, et al. The association between urinary benzophenone concentrations and personal care product use in Korean adults. Arch Environ Contam Toxicol 2016;70(4):640–646. 26626599.

17. Zamoiski RD, Cahoon EK, Michal Freedman D, Linet MS. Self-reported sunscreen use and urinary benzophenone-3 concentrations in the United States: NHANES 2003-2006 and 2009-2012. Environ Res 2015;142:563–567. 26298557.

18. Harley KG, Kogut K, Madrigal DS, Cardenas M, Vera IA, Meza-Alfaro G, et al. Reducing phthalate, paraben, and phenol exposure from personal care products in adolescent girls: findings from the HERMOSA intervention study. Environ Health Perspect 2016;124(10):1600–1607. 26947464.

19. Korean National Institute of Environmental Research. Guidelines for Using Raw Materials for Korean National Environmental Health Survey (Adult): the Fourth Stage (2018–2020) Incheon, Korea: Korean National Institute of Environmental Research; 2022.

20. Park M, Kim S, Kim Y, Nam DJ, Ryoo JH, Lim S. Relationship between personal care products usage and triclosan exposure: the second Korean National Environmental Health Survey (KoNEHS 2012-2014). Ann Occup Environ Med 2019;31(1):2. 30705759.

21. Schneider SL, Lim HW. Review of environmental effects of oxybenzone and other sunscreen active ingredients. J Am Acad Dermatol 2019;80(1):266–271. 29981751.

22. Gago-Ferrero P, Díaz-Cruz MS, Barceló D. UV filters bioaccumulation in fish from Iberian river basins. Sci Total Environ 2015;518-519:518–525. 25777957.

23. Langford KH, Reid MJ, Fjeld E, Øxnevad S, Thomas KV. Environmental occurrence and risk of organic UV filters and stabilizers in multiple matrices in Norway. Environ Int 2015;80:1–7. 25827264.

24. Kim Y, Park M, Nam DJ, Yang EH, Ryoo JH. Relationship between seafood consumption and bisphenol A exposure: the Second Korean National Environmental Health Survey (KoNEHS 2012-2014). Ann Occup Environ Med 2020;32(1)e10. 32411375.

25. Wang J, Pan L, Wu S, Lu L, Xu Y, Zhu Y, et al. Recent advances on endocrine disrupting effects of UV filters. Int J Environ Res Public Health 2016;13(8):782. 27527194.

26. Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, et al. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev 2009;30(4):293–342. 19502515.

27. Pollack AZ, Buck Louis GM, Chen Z, Sun L, Trabert B, Guo Y, et al. Bisphenol A, benzophenone-type ultraviolet filters, and phthalates in relation to uterine leiomyoma. Environ Res 2015;137:101–107. 25531814.

28. Peinado FM, Ocón-Hernández O, Iribarne-Durán LM, Vela-Soria F, Ubiña A, Padilla C, et al. Cosmetic and personal care product use, urinary levels of parabens and benzophenones, and risk of endometriosis: results from the EndEA study. Environ Res 2021;196110342. 33069703.

29. Lee J, Kim S, Park YJ, Moon HB, Choi K. Thyroid hormone-disrupting potentials of major benzophenones in two cell lines (GH3 and FRTL-5) and embryo-larval zebrafish. Environ Sci Technol 2018;52(15):8858–8865. 29995391.

30. Kim S, Kim S, Won S, Choi K. Considering common sources of exposure in association studies - urinary benzophenone-3 and DEHP metabolites are associated with altered thyroid hormone balance in the NHANES 2007-2008. Environ Int 2017;107:25–32. 28651165.

31. Phiboonchaiyanan PP, Busaranon K, Ninsontia C, Chanvorachote P. Benzophenone-3 increases metastasis potential in lung cancer cells via epithelial to mesenchymal transition. Cell Biol Toxicol 2017;33(3):251–261. 27796700.

32. Zhang Y, Mustieles V, Williams PL, Yland J, Souter I, Braun JM, et al. Prenatal urinary concentrations of phenols and risk of preterm birth: exploring windows of vulnerability. Fertil Steril 2021;116(3):820–832. 34238571.

33. Philippat C, Mortamais M, Chevrier C, Petit C, Calafat AM, Ye X, et al. Exposure to phthalates and phenols during pregnancy and offspring size at birth. Environ Health Perspect 2012;120(3):464–470. 21900077.

34. Binder AM, Corvalan C, Calafat AM, Ye X, Mericq V, Pereira A, et al. Childhood and adolescent phenol and phthalate exposure and the age of menarche in Latina girls. Environ Health 2018;17(1):32. 29615064.

35. Kerr AC, Niklasson B, Dawe RS, Escoffier AM, Krasteva M, Sanderson B, et al. A double-blind, randomized assessment of the irritant potential of sunscreen chemical dilutions used in photopatch testing. Contact Dermat 2009;60(4):203–209.

36. Russo JP, Ipiña A, Palazzolo JF, Cannavó AB, Piacentini RD, Niklasson B. Photoallergic contact dermatitis to sunscreens containing oxybenzone in La Plata, Argentina. Actas Dermosifiliogr (Engl Ed) 2018;109(6):521–528. 29655482.

37. Cheng HS, Konya J, Lobel E, Fernandez-Penas P. Patch testing for cheilitis: a 10-year series. Dermatitis 2019;30(6):347–351. 31609855.

38. Scheman A, Jacob S, Katta R, Nedorost S, Warshaw E, Zirwas M, et al. Part 2 of a 4-part series hair products: trends and alternatives: data from the American Contact Alternatives Group. J Clin Aesthet Dermatol 2011;4(7):42–46.

39. Gabb HA, Blake C. An informatics approach to evaluating combined chemical exposures from consumer products: a case study of asthma-associated chemicals and potential endocrine disruptors. Environ Health Perspect 2016;124(8):1155–1165. 26955064.

40. Cosmetic Ingredient Review. Amended safety assessment of benzophenones as used in cosmetics Updated 2020. Accessed January 4, 2024. https://www.cir-safety.org/sites/default/files/Benzophenones.pdf .

41. Gustavsson Gonzalez H, Farbrot A, Larkö O. Percutaneous absorption of benzophenone-3, a common component of topical sunscreens. Clin Exp Dermatol 2002;27(8):691–694. 12472548.

42. Li N, Ho W, Wu RSS, Tsang EPK, Ying GG, Deng WJ. Ultraviolet filters in the urine of preschool children and drinking water. Environ Int 2019;133(Pt B)105246. 31675567.

43. Cunha SC, Trabalón L, Jacobs S, Castro M, Fernandez-Tejedor M, Granby K, et al. UV-filters and musk fragrances in seafood commercialized in Europe Union: occurrence, risk and exposure assessment. Environ Res 2018;161:399–408. 29197758.

44. Song S, He Y, Huang Y, Huang X, Guo Y, Zhu H, et al. Occurrence and transfer of benzophenone-type ultraviolet filters from the pregnant women to fetuses. Sci Total Environ 2020;726138503. 32320878.

45. European Commission Scientific Committee on Consumer Safety (SCCS). OPINION on benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) Updated 2021. Accessed January 12, 2024. https://health.ec.europa.eu/system/files/2022-08/sccs_o_247.pdf .

46. Eftekhari A, Hill JT, Morrison GC. Transdermal uptake of benzophenone-3 from clothing: comparison of human participant results to model predictions. J Expo Sci Environ Epidemiol 2021;31(1):149–157. 33303958.

47. Ogiso T, Shiraki T, Okajima K, Tanino T, Iwaki M, Wada T. Transfollicular drug delivery: penetration of drugs through human scalp skin and comparison of penetration between scalp and abdominal skins in vitro. J Drug Target 2002;10(5):369–378. 12442807.

48. Maibach HI, Feldman RJ, Milby TH, Serat WF. Regional variation in percutaneous penetration in man. Pesticides. Arch Environ Health 1971;23(3):208–211. 5123154.

49. Rothe H, Fautz R, Gerber E, Neumann L, Rettinger K, Schuh W, et al. Special aspects of cosmetic spray safety evaluations: principles on inhalation risk assessment. Toxicol Lett 2011;205(2):97–104. 21669261.

50. Bremmer HJ, Prud’homme de Lodder LC, van Engelen JG. Cosmetics Fact Sheet: To Assess the Risks for the Consumer: Updated Version for ConsExpo 4 Bilthoven, NL, USA: National Institute for Public Health and the Environment; 2006.

51. National Institute for Public Health and the Environment. The ConsExpo Spray Model: modeling and experimental validation of the inhalation exposure of consumers to aerosols from spray cans and trigger sprays Updated 2009. Accessed January 12, 2024. http://www.rivm.nl/bibliotheek/rapporten/320104005.pdf .

52. Zhang T, Sun H, Qin X, Wu Q, Zhang Y, Ma J, et al. Benzophenone-type UV filters in urine and blood from children, adults, and pregnant women in China: partitioning between blood and urine as well as maternal and fetal cord blood. Sci Total Environ 2013;461-462:49–55. 23712115.

53. Janjua NR, Kongshoj B, Andersson AM, Wulf HC. Sunscreens in human plasma and urine after repeated whole-body topical application. J Eur Acad Dermatol Venereol 2008;22(4):456–461. 18221342.

54. Wang M, Tan J, Qi Z, Ge X, Li G, Yu Y. A combined study of skin penetration by confocal Raman spectroscopy and human metabolism: a case of benzophenone-3 in sunscreen. Environ Pollut 2024;340(Pt 1)122868. 37926406.

55. Murthy HS, Rao GS. Cardiovascular responses to scalp infiltration with different concentrations of epinephrine with or without lidocaine during craniotomy. Anesth Analg 2001;92(6):1516–1519. 11375836.

56. Matta MK, Florian J, Zusterzeel R, Pilli NR, Patel V, Volpe DA, et al. Effect of sunscreen application on plasma concentration of sunscreen active ingredients: a randomized clinical trial. JAMA 2020;323(3):256–267. 31961417.

57. Watanabe Y, Kojima H, Takeuchi S, Uramaru N, Sanoh S, Sugihara K, et al. Metabolism of UV-filter benzophenone-3 by rat and human liver microsomes and its effect on endocrine-disrupting activity. Toxicol Appl Pharmacol 2015;282(2):119–128. 25528284.

58. Tang L, Lei B, Xu G, Ma J, Lei JQ, Jin SQ, et al. Polybrominated diphenyl ethers in human hair from the college environment: comparison with indoor dust. Bull Environ Contam Toxicol 2013;91(4):377–381. 23873288.

59. Covaci A, Hura C, Gheorghe A, Neels H, Dirtu AC. Organochlorine contaminants in hair of adolescents from Iassy, Romania. Chemosphere 2008;72(1):16–20. 18396311.

60. Connell SJ, Hollis S, Tieszen KL, McMurray JR, Dornan TL. Gender and the clinical usefulness of the albumin: creatinine ratio. Diabet Med 1994;11(1):32–36. 8181249.

SUPPLEMENTARY MATERIALS

Supplementary Table 1

Quartile concentration of benzophenone-3 according to the use of hair products in total, men, and women

aoem-36-e20-s001.xls

Supplementary Table 2

Adjusted odds ratios and 95% confidence interval of use of hair products with 50th percentile concentration of urine benzophenone-3

aoem-36-e20-s002.xls

Article information Continued

Korean Society of Occupational & Environmental Medicine

https://creativecommons.org/licenses/by-nc/4.0/

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Funded by : Soonchunhyang Universityhttps://dx.doi.org/10.13039/501100002560

Funded by : Ministry of Environmenthttps://dx.doi.org/10.13039/501100003562